Farmington Doctor Is Battling Cancer At Genetic Level

John Woike / Hartford Courant

Dr. Pramod Srivastava, right, talks with research assistant Stephanie Floyd and William Corwin, a post doctorate fellow, in the cancer research lab at the University of Connecticut School of Medicine in Farmington. Srivastava, 60, has devoted his life's work to understanding and trying to unlock the mysteries of the human immune system, which he believes holds a cure for cancer.

Dr. Pramod Srivastava, right, talks with research assistant Stephanie Floyd and William Corwin, a post doctorate fellow, in the cancer research lab at the University of Connecticut School of Medicine in Farmington. Srivastava, 60, has devoted his life's work to understanding and trying to unlock the mysteries of the human immune system, which he believes holds a cure for cancer.

(John Woike / Hartford Courant)

JOSEPH A. O'BRIEN JR.Special To The Courant

Connecticut scientist, immunologist, and inventor is fighting ovarian cancer at the cellular level

Some heroes are forged in an instant; for others it takes a lifetime.

Dr. Pramod Srivastava, 60, has devoted his life's work to understanding and trying to unlock the mysteries of the human immune system, which he believes holds a cure for cancer.

Srivastava, scientist, physician, immunologist, inventor and entrepreneur, spends his days at the University of Connecticut School of Medicine in Farmington, studying tumor cells in search of chinks in their genetic armor.

Cancers, simply put, arise from harmful changes in our DNA, the genetic blueprint that we have inherited from our ancestors. That blueprint includes bits of genetic material collected along the way from viruses, bacteria and random mutations that are a part of evolution. For Srivastava: "Cancer is part of evolution."

As such, he and many other scientists now contend, the best way — and perhaps the only way — to defeat cancer is to find and target the harmful errors in our genetic code.

It wasn't known until recently that our DNA, the instruction book for how we are put together, contained roughly six billion biochemical building blocks, arranged in a particular order or sequence. It took more than a decade and several hundred million dollars just to figure that out.

John Woike / Hartford Courant

Farmington, CT 01/19/16 Dr. Pramod Srivastava, a UConn researcher, is credited with the idea/research/solution for personalized vaccine to fight cancer cells early on.

Farmington, CT 01/19/16 Dr. Pramod Srivastava, a UConn researcher, is credited with the idea/research/solution for personalized vaccine to fight cancer cells early on.

(John Woike / Hartford Courant)

In people with cancer, scientists suggested, one or more genetic mutations are hiding somewhere among those 6 billion building blocks, known as nucleotides that also make up cancer cells. Finding that harmful coding error or errors was next to impossible until scientists developed methods for more rapid sequencing.

At the time, Srivastava proposed that every cancer is different, and that finding, and then targeting, the unique genetic make-up of the tumor itself offered the best chance for treating cancer. This was at odds with conventional wisdom of the time, that suggested cancer shared antigens, and once you found them, one treatment might fit all.

Srivastava focused much of his research on so-called heat-shock proteins and their role in immune responses.

In 1994, he and Garo Armen formed Agenus, formerly Antigenics Inc., a biotechnology company in Lexington, Mass. The company produces pioneering immunotherapies, including vitespen, or Oncophage, the world's first cancer vaccine that was approved for use initially in Russia in 2008. The National Institutes of Health and the Food and Drug Administration have approved a large clinical trial of Oncophage's effect against glioblastomas, a deadly brain cancer. The study is ongoing in 40 cancer centers across the United States.

Srivastava is also the lead investigator for an ovarian cancer vaccine trial that has been approved by the FDA and was scheduled to begin in the winter of 2016. The study, which will assess the safety and feasibility of the vaccine Oncolmmunome on 15 to 20 women with ovarian cancer, is being led by Dr. Angela Kueck, a gynecological oncologist at UConn Health. The study will also monitor any clinical activity of OncoImmunome.

Noting perhaps a difference in the production methods of Oncophage and Oncolmmunome that only an immunologist would appreciate, Srivastava said that while both were made directly from each patient's cancer, the latter is made from the exact sequence of proteins found on the exterior of each patient's cancer cells. Both are personalized cancer vaccines — made specifically for one cancer patient.

UConn bioinformatics engineer Ion Mandoiu, associate professor of computer science and engineering, is a co-investigator for the latest ovarian cancer trial, which took four years to put together.

"This research," Srivastava said, "will serve as the basis for the first ever genomics-driven personalized medicine clinical trial in immunotherapy of ovarian cancer."

Srivastava's seemingly tireless and well-reasoned pursuit of an immunologic cure for cancer has taken him from India, where he was born, to Japan and back to India, where he earned a doctorate in biochemistry at the Center for Cellular and Molecular Biology in Hyderabad. It was there that for the first time he saw a cancer cell under an electron microscope. He completed post-doctoral training at Yale University in New Haven and the Sloan-Kettering Institute for Cancer Research in New York. He is a professor of immunology the University of Connecticut School of Medicine in Farmington where he earned a medical degree and he directs the Center for Immunotherapy of Cancer and Infectious Diseases and the Carole and Ray Neag Comprehensive Cancer Center.

Srivastava's reputation is widely known in the growing field of cancer immunotherapy. But unless you're interested in cancer research or the business of medicine, or happen to bump into Srivastava at a cancer research symposium, chances are you have never heard of him, or of Kueck or Mandoiu. They toil in nondescript laboratories and offices generally far from the limelight.

Caroline Eudy of West Hartford, coordinator of the National Ovarian Cancer Coalition's Connecticut chapter, said the state organization supports the research work done at the Neag Cancer Center.

Eudy, whose mother died of cancer when Eudy was a child, said the clinical trial is offered to women who have previously finished the standard course of treatment for the disease, which generally includes surgery and chemotherapy.

While surgery, chemotherapy and radiation treatments have helped many overcome their cancers, especially in cases where the disease is caught early and remains relatively contained, they are not the final answer, Srivastava said.

"The current treatments are not curing any cancers," said Srivastava who finds relaxation in meditating, playing tennis and kickboxing. "None of these are specific for ovarian cancer. There are all kinds of side effects. They kill cancer and also kind of kill normal tissue."

Srivastava said progress has already been made in trying to prevent cancer, including a vaccine against the Human Papilloma Virus, that's been linked to cervical penile and throat cancer. "We've put our attention on prevention," he said.

Srivastava said his vaccine is being developed for people unlucky enough to already have cancer. "With cancer vaccines," Srivastava said, "we are trying to prevent a recurrence of the disease."